Evaluation of Pharmacokinetic / Pharmacodynamic Data and Interest Individualized Therapeutic Drug Monitoring Glycopeptides and β-lactam-aminoglycoside ICU

NCT02846298 | Unknown DMC

• 1 other identifier: PKPD AG-BL
• Study Type: observational
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

Since the discovery of streptomycin in 1944, aminoglycosides retain a remarkable bactericidal activity vis-à-vis including aerobic gram-negative bacilli. Thus, their synergistic effect with beta-lactams and their rapid bactericidal on many make unavoidable pathogens and make it a cornerstone of the treatment of patients with severe sepsis or state of septic shock. This is antibiotics exclusively parenteral administration. Their effectiveness is concentration-dependent and are administered by 30-minute infusion. Tolerance of venous is usually excellent. Their potential nephrotoxicity or cochleovestibular toxicity requires accurate monitoring of antibiotic residuals. Moreover the fact that the effectiveness of the aminoglycosides is concentration dependent, the rate at the peak is decisive. A first sub-therapeutic dose leads to adaptively resistant bacteria compared to the aminoglycoside and therefore an increase of Minimal Inhibitory Concentrations (MIC). Many studies have been conducted in patients hospitalized in intensive care, highlighting underdoses in aminoglycosides when the prescribed dosages consistent with those used in non reanimated patients. Dr Moore showed in 89 ICU patients with bacteremia gram-negative bacilli, the relationship between the clinical course and obtaining whether therapeutic levels during the first administration of aminoglycosides. Thus, mortality in patients whose antibiotic concentrations to peak were subtherapeutic, amounted to 20.9% against 2.4% when concentrations were within the therapeutic range. In the context or an initial peak in the PK / PD ( Pharmacokinetic / Pharmacodynamic) objectives namely Cmax / MIC ≥ 8-10 desirable, individualized therapeutic drug monitoring and identification of factors that may cause a concentration of antibiotic at sub-therapeutic peak seems necessary , in patients for the majority an increased volume of distribution. In addition to the β-lactams and glycopeptides, due to the increased volume of distribution in critically ill patients in sepsis, evaluation of serum 24 hours after starting treatment to check that the PK / PD goals for these molecules is achieved.

Conditions

Severe Infection

Keywords

Drug Monitoring; ICU; Pharmacokinetic; Pharmacodynamic; antibiotic; Glycopeptides; β-lactam-aminoglycoside

Outcome Measures

Primary Outcomes (4)

• Assessment of Pharmacokinetic Glycopeptides Cmax

  Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses

  30 minutes after first injection

• Assessment of Pharmacodynamic Glycopeptides Cmax

  Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses

  30 minutes after first injection

• Assessment of Pharmacokinetic β-lactam-aminoglycoside Cmax

  Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses

  30 minutes after first injection

• Assessment of Pharmacodynamic β-lactam-aminoglycoside Cmax

  Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses

  30 minutes after first injection

Secondary Outcomes (3)

• Mortality rate

  Day 30

• Assess the residual of Glycopeptides

  Hour 12 and Hour 24 after injection

• Assess the residual of β-lactam-aminoglycoside

  Hour 12 and Hour 24 after injection

Interventions

Drug Monitoring BIOLOGICAL

Evaluation of Pharmacokinetic / Pharmacodynamic Data and Interest Individualized Therapeutic Drug Monitoring Glycopeptides and β-lactam-aminoglycoside ICU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All adult patients ≥ 18 years admitted to the intensive care unit of GH Paris Saint-Joseph and who will prescribe the entrance or during their stay an aminoglycoside treatment for severe infection

You may qualify if:

• Age w\< 18 years old
• admitted in ICU unit for whom aminoglycoside treatment for severe infection was prescribed

You may not qualify if:

• Age less than 18 years
• Treatment with aminoglycoside off label
• Patient non hospitalized in intensive care

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead

Study Sites (1)

Groupe Hospitalier Paris Saint Joseph

Paris, Île-de-France Region, 75014, France

Location

MeSH Terms

Conditions

Infections

Interventions

Prescription Drug Monitoring Programs

Intervention Hierarchy (Ancestors)

Product Surveillance, Postmarketing; Evaluation Studies as Topic; Investigative Techniques; Drug Information Services; Pharmaceutical Services; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Philippart Francois, MD

  Fondation Hôpital Saint-Joseph

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: July 27, 2016
• Study Start: November 8, 2015
• Primary Completion: October 22, 2018
• Study Completion: December 31, 2023
• Last Updated: April 27, 2023

Record last verified: 2023-04

Locations

FR (1)